title: o-p'-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague-Dawley rats.
abstract: 1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p'-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague-Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p'-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p'-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy.
authors.affiliation: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, USA; Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Kwekel
authors.forename: Agnes L
authors.initials: AL
authors.lastname: Forgacs
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Williams
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Zacharewski
mesh_terms: D000818:Animals; D003634:DDT / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010575:Pesticides / Q000633:toxicity*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D052244:Endocrine Disruptors; D004967:Estrogens; D010575:Pesticides; D011960:Receptors, Estrogen; D012313:RNA; D003634:DDT; C016340:o,p'-DDT
keywords: Cross-species; DDT; Estrogen receptor; Toxicogenomics; Uterus